Causal associations between estradiol and mouth ulcers: A Mendelian randomization study.

People have difficulty in eating and speaking when they are suffering from mouth ulcers. Some studies suggest that estradiol is associated with the development and treatment of mouth ulcers, while some do not. To clarify the effect of estradiol on mouth ulcers, we performed 2-sample Mendelian randomization and multivariable Mendelian randomization (MVMR) analysis to evaluate their relationship. Data were obtained from the IEU OpenGWAS project and UK biobank, including male estradiol dataset (case/controls = 13,367/134,323), female estradiol dataset (case/controls = 37,461/126,524), mouth ulcers dataset (case/controls = 47,102/414,011). The causal associations were estimated by MR-Egger, weighted median, inverse-variance weighted (IVW) method, simple mode, and weighted mode. Cochran Q test, MR-Egger intercept test, MR-PRESSO tests, and leave-one-out analysis were used to examine sensitivity analyses. The MVMR controlling for depression, anxiety or panic attacks, severe stress and adjustment disorders was used to assess the effect of estradiol on mouth ulcers. Through screening, 13 single nucleotide polymorphisms (SNPs) of males and 2 SNPs of females in estradiol were used for harmonizing and MR analysis. The 2-sample MR analysis showed no causal association between estradiol of males and mouth ulcers (IVW, OR: 0.998, 95% confidence interval [95% CI]: 0.995-1.001, P = .18). Similar results were obtained between estradiol of females and mouth ulcers (IVW, OR: 1.000, 95% CI: 0.988-1.012, P = .97). No pleiotropy and heterogeneity were found and the results were robust (P > .05). After adjusting for the potential effects of confounders, estradiol of males and mouth ulcers still showed no causal association through MVMR analysis (P = .081). While MVMR analysis showed that the causal relationship between estradiol and mouth ulcers in women could not be statistical for the small number of SNPs. There was no evidence of a causal relationship between estradiol and mouth ulcers. The strategy of treating mouth ulcers with estradiol still needs to be confirmed by more studies.

Chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Who really needs it.

OBJECTIVES: The CSCO and ASCO guidelines in 2021 recommend chemotherapy for stage III-IVA (8th edition of AJCC staging) nasopharyngeal carcinoma (NPC). Actually, patients with stage T3-4N0M0 are often excluded from various clinical trials of the locoregionally advanced NPC, and the survival benefit of chemotherapy in such patients has always been controversial. This study aims to explore the benefit of chemotherapy in patients with locoregionally advanced NPC, especially those with negative lymph nodes. METHODS: A total of 2741 patients were extracted from the SEER database. After a 1:1 PSM analysis, 272 patients were obtained to further explore whether the addition of chemotherapy would achieve survival benefits. RESULTS: After PSM, Kaplan-Meier curves showed that the overall survival (OS) of patients receiving chemoradiotherapy (p = 0.031) was higher than those receiving radiotherapy alone. Similar results were observed for cancer-specific survival (CSS). We further stratified the patients according to lymph node status and found that the addition of chemotherapy in patients with positive lymph nodes could significantly improve 5-year OS rates (58.08% vs. 43.95%; p = 0.025) and 5-year CSS rates (67.42% vs. 51.95%; p = 0.015) compared with radiotherapy alone, but there was no additional benefit of chemotherapy in patients with negative lymph nodes. For all 449 cases of T3-4N0M0 NPC, radiotherapy improved the OS rates (HR 0.293, 95% CI 0.203-0.424) and the CSS rates (HR 0.252, 95% CI 0.171-0.371) compared with no radiotherapy, while chemotherapy did not show significant survival benefit compared with no chemotherapy. CONCLUSION: Our results reveal that stage T3-4N0M0 NPC may be exempted from chemotherapy, and use radiotherapy alone to reduce toxic and side effects. These results still need to be verified by future prospective trials.

The role of surgery on the primary tumor site in bladder cancer with distant metastasis: significance of histology type and metastatic pattern.

Due to the limited data and research on bladder cancer with distant metastasis, the role of surgery on the primary tumor site in metastatic bladder cancer has been controversial. The aim of this study was to investigate the impact of surgery on patients with metastatic bladder cancer and to identify any factors correlated with the treatment efficacy. Using the Surveillance, Epidemiology and End Results dataset, we performed a large population-based retrospective study. We classified patents with distant metastasis into subgroups according to their histology type and metastatic pattern. Propensity score matching (PSM) was used to balance clinical variables bias in a 1:3 ratio. A total of 2470 patients with distant metastasis were identified from 2010 to 2016. After PSM, the study eventually included 1068 patients in the surgery group and 356 patients in the non-surgery group. The histologic types, the number of metastatic sites, liver metastasis, surgery, and chemotherapy were significant prognostic variables for patients with distant metastasis before and after PSM. In terms of histologic types, the survival of patients with transitional cell papillary carcinoma, transitional cell non-papillary carcinoma and adenocarcinoma can be improved by surgery alone, while the survival of patients with squamous cell carcinoma can be improved only by combining chemotherapy and surgery. In terms of the number of metastatic sites, surgery alone was an independent prognostic factor in patients with 1 or 2 metastatic sites. In terms of the specificity of metastatic organs, surgery affected overall survival for patients with bone metastasis only, liver metastasis only and lung metastasis only, but for distant lymph nodes metastasis only. It may be helpful to classify patients with bladder cancer and distant metastasis into different groups by integrating variables including histology types and metastatic patterns to choose appropriate treatment strategies.

Pattern and prognosis of distant metastases in nasopharyngeal carcinoma: A large-population retrospective analysis.

Currently, the features and prognosis of nasopharyngeal carcinoma (NPC) with distant metastases are still rarely reported. Thus, the main purpose of our study was to investigate the metastasis patterns of different histological types of NPC and to clarify the prognostic characteristics of metastases at different sites. Patients were enrolled from the SEER program from 2010 to 2016. Chi-squared tests were used to compare features between groups. The tendency to develop combined metastases was assessed with the odds ratio. The Kaplan-Meier method was used for the survival analysis. Univariate and multivariate Cox analyses were used to select the independent prognostic risk factors for inclusion in the nomogram. In the present study, we found the following: (1) tumors are highly likely to metastasize if they have a larger volume, the regional lymph nodes are relatively large, or the regional lymph nodes are biopsied but not removed; (2) the bone and the brain were the most and least common metastatic sites among all histological types and N stages. Metastasis at two sites was the most common pattern, and bone metastasis was generally associated with metastasis to the liver or brain; (3) the prognostic analyses in metastatic patients showed that cancer-specific survival (CSS) was relatively worse in patients with multiple metastases, and in those with liver metastasis regardless of the number of other metastatic sites; (4) A nomogram was constructed for clinical use based on four independent prognostic risk indicators, including histology, radiation therapy, chemotherapy, and metastatic status. Our findings provide a reference for clinical decision-making and future diagnostic screening tests for NPC with distant metastases.

A network pharmacology-based study on Alzheimer disease prevention and treatment of Qiong Yu Gao.

BACKGROUND AND OBJECTIVE: As the pathological mechanisms of AD are complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach. METHODS: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments. RESULTS: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. The KEGG pathway enrichment analysis found that three signaling pathways were closely related to AD prevention and treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway. CONCLUSION: This study demonstrated that QYG exerted the effect of preventing and treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines.

The effect and mechanism of YH0618 granule on chemotherapy- induced hair loss in patients with breast cancer: study protocol for a randomized, double-blind, multi-center clinical trial.

BACKGROUND: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction. METHODS/DESIGN: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine. DISCUSSION: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.

[Target protein candidates of hypothalamus in aging rats with intervention by Qiongyugao].

To explore the associated proteins of the hypothalamus in aging rat models with intervention by Qiongyugao(QYG) based on iTRAQ technology, find out the target protein candidates and investigate the mechanism of delaying aging for Qiongyugao. The results showed that Qiongyugao increased GSH-Px activity in serum and SOD activity in liver; the total protein count identified by iTRAQ was 3 522, FDR<1%. There were 20 kinds of differential proteins between the blank group and model group; there were 295 kinds of differential proteins between model group and QYG group, and 40 kinds of them had a difference multiple ≥1.30 (the maximum value was 1.47). Compared with blank group, there were 14 kinds of proteins that were down-regulated in model group and up-regulated in QYG group. Combined with literature search and gene function search, 12 kinds of target protein candidates were screened out ： ST18, Ptprc, PSMB8, INPP4B, Shc3, Pik3r1, PIP5K1C, Nampt, Rasgrp2, Asah2, Pdpk1, and Map2k7. The expression of nuclear factor-kappa B (NF-κB) in the hypothalamic inflammatory pathway was detected by Western blot and the results showed that its expression level in model group(0.96) was higher than that in control group(0.85), while its expression level in QYG group(0.89) was lower than that in model group. Q-PCR results showed that the relative mRNA expression levels of PIP5K1C and Ptprc in model group were significantly lower than those in blank group(P<0.01); while compared with the model group, the mRNA expression levels of PIP5K1C and Ptprc in QYG group were significantly increased(P<0.01) . This result was consistent with proteomics data. QYG may delay aging by regulating hypothalamic inflammatory reaction.